This article compares two important pathophysiological states, Kawasaki disease, and multisystem inflammatory syndrome, in children associated with COVID-19 (MIS-C). Both occur predominantly in children, have a temporal association with an infectious agent, and are associated with immune-system alteration and systemic inflammation under certain circumstances. The two share common pathophysiology, including enhancement of interleukin-1 neutrophils, activation of the inflammasome, pyroptosis, or NETosis. Moreover, the clinical presentation of the diseases overlaps. However, they are indeed two separate diseases, proven by the differences in the epidemiological and etiological aspects and the pathophysiological processes involved in the development and frequency of some clinical signs. This article highlights potentially exciting areas that have not yet been studied in detail, which could help better understand the development of these diseases.
Liver cirrhosis is associated with impairment of cardiovascular function including alterations of the heart innervation, humoral and nervous dysregulation, changes in systemic circulation and electrophysiological abnormalities. Choline acetyltransferase (ChAT), enzyme forming acetylcholine, tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DBH), enzymes participating in noradrenaline synthesis, are responsible for the production of classical neurotransmitters, and atrial natriuretic peptide (ANP) is produced by cardiomyocytes. The aim of this study was to evaluate the influence of experimentally induced hepatic dysfunction on the expression of proANP, ChAT, TH, and DBH in the heart. Hepatic dysfunction was induced by application of thioacetamide (TAA) or by ligation of bile duct. Biochemical parameters of hepatic injury and levels of peroxidation in the liver and heart were measured. Liver enzymes measured in the plasma were significantly elevated. Cardiac level of peroxidation was increased in operated but not TAA group animals. In the left atrium of operated rats, the expression of TH and DBH was lower, while expression of ChAT remained unchanged. In TAA group, no significant differences in the expression of the genes compared to controls were observed. Liver injury induced by ligation leads to an imbalance in the intracardiac innervation, which might impair nervous control of the heart.
MUC13, a transmembrane mucin glycoprotein, is overexpressed in colorectal cancer (CRC), however, its regulation and functions are not fully understood. It has been shown that MUC13 protects colonic epithelial cells from apoptosis. Therefore, studying MUC13 and MUC13-regulated pathways may reveal promising therapeutic approaches for CRC treatment. Growing evidence suggests that microRNAs (miRs) are involved in the development and progression of CRC. In the present study, the MUC13-miR-4647 axis was addressed in association with survival of patients. miR-4647 is predicted in silico to bind to the MUC13 gene and was analyzed by RT-qPCR in 187 tumors and their adjacent non-malignant mucosa of patients with CRC. The impact of previously mentioned genes on survival and migration abilities of cancer cells was validated in vitro. Significantly upregulated MUC13 (P=0.02) in was observed tumor tissues compared with non-malignant adjacent mucosa, while miR-4647 (P=0.05) showed an opposite trend. Higher expression levels of MUC13 (log-rank P=0.05) were associated with worse patient's survival. The ectopic overexpression of studied miR resulted in decreased migratory abilities and worse survival of cells. Attenuated MUC13 expression levels confirmed the suppression of colony forming of CRC cells. In summary, the present data suggested the essential role of MUC13-miR-4647 in patients' survival, and this axis may serve as a novel therapeutic target. It is anticipated MUC13 may hold significant potential in the screening, diagnosis and treatment of CRC.
Observational studies in human patients and animal experiments suggested that statins have a potential in slowing the growth of small abdominal aortic aneurysms (AAA). Our aim was to quantify histological postoperative changes of AAA in porcine experimental model of AAA with and without administration of atorvastatin.The AAA was induced by intraaortic infusion of porcine pancreatic elastase and subrenal application of plastic cuff. The AAA statin group (N.=14) received atorvastatin 1 mg/kg daily for 28 days, the other AAA group (N.=13) did not. The aortic diameter was measured by ultrasonography. Aortic samples were described using eleven quantitative histological parameters and compared with healthy aortae.There was no difference in aortic diameter between the AAA with statin when compared to AAA without statin. Administration of atorvastatin led to a better postoperative histological condition of the aortic elastin network, preservation of contractile phenotype of vascular smooth muscle, a higher density of vasa vasorum, it prevented thickening of intima and media. The increase in wall thickness in AAA without atorvastatin has not been accompanied by a proportional increase in number of vasa vasorum.The effects of atorvastatin seem to prevent the histopathological progression of AAA.
<i>Background:</i> Many studies have been performed in order to model abdominal aortic aneurysm (AAA) in an experimental animal, most commonly in small laboratory animals. In our study, we tried to find the best AAA model in a pig by using various mechanical and enzymatic mechanisms. <i>Methods:</i> Twenty-two pigs were operated on. We combined 3 mechanisms of creating an AAA, using an intraluminal infusion of porcine pancreatic elastase into the abdominal aortic segment, application of plastic cuff below the renal arteries causing turbulent blood flow, and inserting a patch into the longitudinal aortotomy. <i>Results:</i> We found different results in different groups according to the mechanisms used. In group A, with a combination of the intraluminal elastase infusion and application of a stenosing cuff, AAA developed in all 7 animals (100%). In this group, we also found the largest histological changes in the abdominal aorta samples. <i>Conclusion:</i> The use of intraluminal pancreatic elastase infusion, together with increased turbulent flow caused by the stenosing cuff, seems to be the best model of AAA in pigs. This model is suitable for further research in the etiopathology of AAA. In fact, it is the first successful approach to a large-caliber native aneurysm model.
Abstract The proteins of the fibrinolytic system — urokinase plasminogen activator(uPA), tissue plasminogen activator (tPA)and plasminogen activator inhibitor type IPAI-I) — play important roles in fibrotization in various organs and including peritoneum. To study the cellular localization of PAI-1, tPA and uPA within the adipose tissue of the peritoneal membrane in patients at the onset of peritoneal dialysis(PD) we determined the initial expression of these proteins in relationship to multiple clinical variables. Methods: routinely performed parietal peritoneal biopsies in 12 patients undergoing peritoneal catheter implantation were examined. We used formalinfixed, paraffin-embedded specimens for immunohistochemical localization of these proteins along with the stereological pointcounting method for quantification of their expression within the peritoneal adipose tissue. Results: strong positive mutual correlation between the expression of PAI-1 and both uPA (SpearmanR=0.66) and tPA (R=0.59) as well as between the expression of uPA and tPA (R=0.77) was found without any relatioship to BMI, age, peritoneal transport characteristic or diabetes status. Conclusion: Adipose tissue within the peritoneum is capable of producing fibrinolysis regulators (independently on clinical parameters) thus possibly affecting the fibrotization and function of peritoneum as dialysis membrane. The effect of dialysis solution dosing, composition and other dialysis related factors should be clarified in future studies.
